Interference between pathway‐specific transcription factors: glucocorticoids antagonize phorbol ester‐induced AP‐1 activity without altering AP‐1 site occupation in vivo.

Phorbol esters stimulate and glucocorticoid hormones down‐regulate a variety of promoters such as that of the collagenase gene through the transcription factor AP‐1 (Fos/Jun). We now show by genomic footprinting of the collagenase promoter that phorbol ester treatment of cells results in the binding of AP‐1 to its cognate DNA binding site in vivo. The DNA‐protein contacts obtained in living cells are also found in vitro using cloned DNA and purified AP‐1. Although in vitro synthesized glucocorticoid receptor can disturb the DNA binding of Jun homodimers, it does not interfere with the binding of Fos‐Jun heterodimers or of purified AP‐1 in vitro. Consistently, fully inhibitory doses of glucocorticoid hormone cause no change in apparent occupation of the AP‐1 binding site in vivo. The hormone receptor acts without itself binding to DNA.